MicroRNA-494 regulates Gli3 expression and inhibits pancreatic cancer cells growth and migration

J Cell Biochem. 2018 Jul;119(7):5324-5331. doi: 10.1002/jcb.26658. Epub 2018 Mar 25.

Abstract

MicroRNA (miR)-494 has been identified as a predictor and inhibitor in pancreatic cancer. This study aimed to explore the role of miR-494 in pancreatic cancer cells, and the regulation of glioma-associated oncogene 3 (Gli3) by miR-494. The mRNA level of Gli3 in 99 pairs of pancreatic cancer and correspondingly adjacent tissues was monitored by qRT-PCR. Correlation of Gli3 expression with miR-494 level was assessed by Pearson χ2 test. Dual-luciferase reporter assay was used to detect whether Gli3 was a target of miR-494. Following miR-494 mimics and miR-494 inhibitor transfection, the changes in cell viability and migration were detected by using CCK-8 and Transwell chamber. Furthermore, Gli3 siRNA was co-transfected with miR-494 inhibitor, and then cell viability and migration were redetected. Result showed that, the mRNA level of Gli3 in tumor tissues was higher than in the adjacent tissues (P < 0.01). There were 45 in 99 patients with pancreatic cancer expressed Gli3, and significant correlations were observed between the Gli3 level and vascular invasion (P = 0.04), distant metastasis (P = 0.001), and histologic grade (P = 0.03). Gli3 was a direct target of miR-494 (P < 0.01) and it was negatively related by miR-494 (P < 0.01). Overexpression of miR-494 suppressed PANC-1 cells viability (P < 0.05, P < 0.01, or P < 0.001) and migration (P < 0.01). Additionally, Gli3 silence suppresses miR-494 suppression-induced cell viability and migration (P < 0.01). In conclusion, these data demonstrate miR-494 exhibits tumor-suppressive effects on pancreatic cancer, possibly via targeting Gli3.

Keywords: cell migration; cell viability; glioma-associated oncogene 3 (Gli3); microRNA-494; pancreatic cancer.

Publication types

  • Retracted Publication

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Tumor Cells, Cultured
  • Zinc Finger Protein Gli3 / genetics
  • Zinc Finger Protein Gli3 / metabolism*

Substances

  • Biomarkers, Tumor
  • GLI3 protein, human
  • MIRN494 microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • Zinc Finger Protein Gli3